This invention relates to ophthalmic, otic and nasal suspension formulations containing water-insoluble resins as drug delivery aids. In particular, this invention relates to the use of combinations of polymeric suspending agents to improve the physical stability of suspension formulations containing water-insoluble drug delivery aids.
U.S. Pat. No. 4,911,920, the entire contents of which are incorporated by reference, discloses sustained release formulations for glaucoma therapy, wherein the formulations comprise a basic active and a cationic exchange resin dispersed in an aqueous solution or gel of a polyanionic polymer. The cationic-exchange resin in the '920 formulations can be “any pharmaceutical grade cationic exchange resin” (Col. 3, lines 65–66 of the '920 patent) and include the “Amberlite” (Rohm & Haas) and “Dowex” (Dow Chemical Co.) lines of commercially available resins. The polyanionic polymers have a molecular weight of from about 50,000 to about 6 million, and are characterized as having carboxylic acid functional groups. Preferred polyanionic polymers are the carboxy vinyl polymers known as carbomers, such as those available under the trade name Carbopol from the B.F. Goodrich Company. Carbopol 934 and Carbopol 940 are specifically preferred.
U.S. Pat. No. 5,188,826 discloses an ophthalmic gel suspension for treating dry eye. The suspension formulations remain as a gel in the eye for a prolonged time, and release water and one or more ophthalmic demulcents or vasoconstrictors. The suspension formulations contain a water-insoluble, lightly cross-linked, carboxyl-containing polymer having a particle size of not more than 50 μm in equivalent spherical diameter. The demulcent is preferably at least one of sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, dextran 70, gelatin, glycerin, polyethylene glycol, polysorbate 80, propylene glycol, polyvinyl alcohol or polyvinylpyrrolidone. Particularly preferred as the carboxyl-containing polymer is Carbopol 976. The suspension formulations do not contain a prescription drug.
U.S. Pat. No. 5,192,535 discloses suspension formulations of ophthalmic drugs that have suitably low viscosities to permit easy administration in drop form, but which rapidly gel in the eye to provide sustained drug release. The suspension formulations are formulated at a pH of from about 3 to about 6.5 and contain a water-insoluble, carboxyl-containing polymer prepared by polymerizing one or more carboxyl-containing monethylenically unsaturated monomers and less than about 5% by weight of a cross-linking agent. Carbopol 976 and polycarbophil are identified as examples of suitable carboxyl-containing polymers. Ion exchange resins may be included as one type of adjuvant in the suspension formulations. Demulcents are identified as one of many types of medicaments suitable for use in the suspension formulations.
WO 92/11871 discloses suspension formulations for controlled delivery of pharmaceutical compounds. The sustained release compositions are generally formed as follows. First, one or more pharmaceutical compounds are reversibly loaded onto ion exchange resin particles. Second, the loaded ion exchange resin particles are incorporated into an erodible polymeric complex. The polymeric matrix coating incorporating the loaded ion exchange resin particle at least partially encloses the loaded exchange resin particle as either a solid matrix or enclosing microcapsule. Preferably, the polymeric matrix will totally enclose at least one or more of the drug-loaded ion exchange resin particles. In this manner, the loaded pharmaceutical compound is locked into the ion exchange resin particle and shielded from external solvent effects, enhancing chemical stability and storage stability, for example. The polymer matrix may be formed from any phsiologically compatible erodible polymer. The polymers should be substantially non-ionic. Preferred exemplary polymers include polyvinylpyrrolidone, poly(methylvinylether/maleic anhydride) and mixtures thereof. Incorporation of the loaded ion exchange resin particles into the polymeric matrix may be accomplished through a variety of methods, including precipitation and phase coacervation techniques.